Fusobacterium nucleatum promotes tumor progression driven by histone lactylation through increasing GLUT1 expression in colorectal cancer

The gut microbiota plays a significant role in the incidence and progression of colorectal cancer（CRC）, with Fusobacterium nucleatum (F. nucleatum) identified as a contributor to the advancement of this malignancy. However, the precise mechanisms underlying its action remain unclear. This study uses FISH technology to measure F. nucleatum in tumors and WB to examine histone lactylation, exploring their connection. HCT116 CRC cells were treated with lactic acid, Oxamate, 2-DG, and F. nucleatum supernatant to analyze histone lactylation and cell behaviors like proliferation, migration, and invasion. The research also screened F. nucleatum supernatant for compounds that increase tumor cell lactylation and assessed their effects on cell viability using CCK-8, EdU, and transwell assays. Additionally, GLUT agonists and inhibitors were used to demonstrate that formic acid in the supernatant elevates GLUT1 expression. Tumors characterized by elevated nuclear levels demonstrate increased histone lactylation. Modulating histone lactylation levels in tumor cells through human intervention can substantially impact their proliferative, migratory, and invasive capacities. Our study identified that F. nucleatum enhances the expression of GLUT1 in tumor cells via its metabolite, formic acid, leading to increased lactate production and histone lactylation. This process ultimately augments the stemness of tumor cells. F. nucleatum enhances the expression of GLUT1 in colorectal cancer cells through the production of formic acid, which subsequently elevates histone lactate levels and facilitates tumor progression.